Ginkgo biloba is the oldest living tree species on Earth — it is a relict species that survived the last ice age and that has been used in traditional Chinese medicine for over 3,000 years for the treatment of asthma, tinnitus (ringing in the ears), and poor circulation. The Ginkgo extract (GBE) that is used in modern supplements is a standardised preparation of the leaves of the Ginkgo biloba tree, containing 24% flavonoids (primarily the flavonol glycosides quercetin, kaempferol, and isorhamnetin) and 6% terpene lactones (primarily the ginkgolides A, B, and C and the bilobalide). The therapeutic effects of Ginkgo are attributed to these flavonoid and terpene lactone compounds, which have vasodilatory, anti-inflammatory, antioxidant, and neuroprotective effects that are the basis for its use in the treatment of cognitive impairment, of age-related cognitive decline, of the cognitive deficits of the dementia syndrome, and of the tinnitus and the vertiginous syndromes that are associated with poor cerebral blood flow.
GBE and Cerebral Blood Flow
The primary mechanism by which Ginkgo improves cognitive function is through the enhancement of cerebral blood flow — it dilates the blood vessels of the brain, reduces the resistance to blood flow in the cerebral circulation, increases the delivery of oxygen and glucose to the brain tissue, and thereby improves the cerebral metabolism that is essential for cognitive function. The vasodilatory effect of Ginkgo is mediated primarily by the ginkgolides — particularly ginkgolide B, which is a potent antagonist of the platelet-activating factor (PAF) receptor. PAF is a potent vasoconstrictor and platelet-activating factor that is released by the endothelial cells and the immune cells during inflammation and that produces vasoconstriction and platelet aggregation in the cerebral circulation. By blocking the PAF receptor, ginkgolide B reduces the PAF-induced vasoconstriction and platelet aggregation and thereby improves the blood flow to the brain. The flavonoid components of Ginkgo also contribute to the vasodilatory effect through their stimulation of the endothelial production of nitric oxide (NO), the potent vasodilator that is produced by the endothelial nitric oxide synthase (eNOS) enzyme in response to the shear stress of blood flow and in response to inflammatory cytokines.
The clinical importance of the cerebral vasodilatory effect of Ginkgo is most clearly demonstrated in the treatment of the cognitive symptoms that are associated with poor cerebral circulation — including the vertigo, the tinnitus, the memory impairment, and the reduced attention span that are characteristic of the vascular cognitive impairment syndrome. The randomised controlled trials of Ginkgo in people with age-related cognitive decline or with mild cognitive impairment (MCI) have shown modest but statistically significant benefits in cognitive function (with effect sizes of approximately 0.2-0.3 SD units in the meta-analyses), and the benefits are most pronounced in people with the cognitive symptoms that are associated with poor cerebral circulation. The MAELES trial (2016, in 2,854 older adults with normal cognitive function) found no benefit of Ginkgo on the incidence of dementia or on the rate of cognitive decline over 7 years of follow-up — a finding that is consistent with the hypothesis that Ginkgo is most effective for the cognitive symptoms that are secondary to impaired cerebral blood flow, rather than for the primary neurodegenerative processes that cause the Alzheimer-type dementia syndrome.
GBE and Neuroprotection
Beyond its effects on cerebral blood flow, Ginkgo also has direct neuroprotective effects that are mediated through its antioxidant activity (the flavonoids neutralise the ROS that are generated by the impaired mitochondria of the ageing neurons), through its anti-inflammatory effects (the ginkgolides inhibit the NF-kappaB and COX-2 pathways that mediate the neuroinflammation of the ageing brain), and through its anti-amyloid effects (bilobalide, the unique terpene lactone of Ginkgo, has been shown to reduce the production and the aggregation of the amyloid-beta peptides that are the pathological hallmark of the Alzheimer brain). These neuroprotective effects are complementary to the cerebral vasodilatory effect and together they explain the broad spectrum of the cognitive benefits that are attributed to Ginkgo in traditional use and in the clinical trials.
Practical Application
For general Ginkgo supplementation, the evidence-based dose is 120-240mg of standardised Ginkgo biloba extract (containing 24% flavonoids and 6% terpene lactones) daily, divided into two or three doses. The evidence for the cognitive benefits of Ginkgo is strongest in people with the cognitive symptoms that are associated with impaired cerebral blood flow (vertigo, tinnitus, memory impairment, reduced attention span), and it is weaker in people with primary neurodegenerative dementia (Alzheimer disease, vascular dementia). Ginkgo is generally well-tolerated with no significant adverse effects at doses up to 240mg daily, though it may increase the bleeding risk in people who are taking anticoagulant or antiplatelet drugs (warfarin, aspirin, clopidogrel) because of its antiplatelet effect. For comprehensive cognitive and cerebral blood flow support, Ginkgo pairs well with the omega-3 fatty acids (which support the neuronal membrane function and which have anti-inflammatory effects), with acetyl-L-carnitine (which supports neuronal mitochondrial function), with phosphatidylserine (which supports the neuronal membrane protein function), and with Bacopa monnieri (which supports memory formation through a different mechanism).
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